The study shows that mouse adrenal cells have the MC4‑receptor and make a protein called AgRP, and that stimulating these cells with a melanocortin peptide (similar to melanotan‑I) or with a chemical that raises cAMP lowers the amount of MC4‑receptor over time. Leptin, a hormone linked to fat, doesn’t change MC4‑receptor levels but does lower another receptor (MC2‑R). In obese mice, both receptors are reduced while AgRP goes up, hinting that body‑fat status can affect this adrenal system.

Adrenocortical cells of several species have been reported to express significant levels of Agouti-related protein (Agrp) as well as melanocortin 4-receptor (MC4-R). In this study, we used the mouse tumoral adrenal cell line ATC7- L that secretes corticosterone in basal conditions with a 2- fold increase in response to ACTH treatment. We reported that these cells expressed functional MC4-R. They also expressed Agrp mRNA and secreted immunoreactive Agrp in the culture medium. Long-term treatment of ATC7-L with (Nle4,D-Phe7)-alpha MSH (NDP-alpha MSH) or forskolin as well as Agrp strongly reduced MC4-R level by more than 30%. On the contrary, leptin treatment did not modify this level although it significantly reduced MC2-R level. These results could be correlated to some data obtained in vivo on adrenal glands removed from diet-induced obese mice exhibiting a hyperleptinemia, where the level of both MC2-R and MC4-R appeared to be reduced as Agrp mRNA expression level was increased compared to Control mice. All these data would suggest the existence of a link between the metabolic status and the activation of the adrenal melanocortinergic system.